Protein linked to elevated BMI in people of American Indian, Mexican ancestry

University of Minnesota researchers have discovered a variant of a common blood protein, apolipoprotein C1, in people of American Indian and Mexican ancestry that is linked to elevated body mass index (BMI), obesity and Type 2 diabetes.

The finding were published in the Feb. 20 online issue of the International Journal of Obesity.

Lead investigator Gary Nelsestuen, a professor in the College of Biological Sciences' department of biochemistry, said the abnormal protein may promote metabolic efficiency and storage of body fat when food is abundant. This could have provided a survival advantage to American Indians in the past when food was scarce. The discovery can be used to identify those who are at risk for diabetes and to guide diet and lifestyle choices to prevent diabetes.

Apolipoprotein C1 is a component of high density lipoprotein (HDL) and low density lipoprotein (LDL). HDL cholesterol is often referred to as good cholesterol, while LDL is called bad cholesterol. The common form of C1 tends to be found in the high-density protein complexes (HDL) that ferry cholesterol to storage depots in the body and are linked to lower cardiovascular disease risk. But the variant form of C1 tends to become part of low density protein complexes (LDL), which transport cholesterol to arterial walls and are associated with higher cardiovascular disease risk. Thus, having the variant could tip the balance of cholesterol carriers and lead toward depletion of HDL-also a risk factor for heart disease. The variant differs from the normal protein by a single change in one of its 57 amino acids.

Among 1500 subjects from widely divergent genetic backgrounds, the variant was found in 35 of 228 persons with American Indian ancestry and in 10 of 84 persons with Mexican ancestry. The average body mass index (BMI) of persons with the variant protein was 9 percent higher and the diabetes rate 50 percent higher among study subjects and their parents. Parents were included because type 2 diabetes often doesn't appear until later in life.

Advertisement

This project has been a departure for Nelsestuen, who has made important discoveries related to blood coagulation proteins involved in bleeding disorders such as hemophilia and coagulation disorders such as sepsis and thrombosis. The university has licensed these proteins to three pharmaceutical companies who are developing them as therapeutic agents. Nelsestuen is recognized on the university's Wall of Discovery for some of these achievements.

Nelsestuen used income from the blood coagulation protein licenses and his endowment from the Samuel Kirkwood Chair to support the research that led to finding the abnormal variant of C1 lipoprotein.

The funds were used to apply new proteomics technology to screen blood samples for proteins related to disease. This type of protein screening is often described as "discovery" research. In its purest form, proteomics discovery research looks for abnormal proteins in what seems like a random process.

"This type of research is often dismissed as a fishing expedition by funding agencies," Nelsestuen said. "But our finding shows the value of discovery research and of having unrestricted funds to pursue it."

Nelsestuen's interest in education of minority graduate students provided many of the connections to the communities that became involved in this research. Former student Michael Martinez, helped establish a collaboration with Kenneth McMillan, medical director of the American Indian Community Development Corporation in Minneapolis, and Cristina Flood-Urdangarin of St. Mary's Health Clinics in St. Paul.

Nelsestuen's next steps will be to expand the study to the Turtle Mountain Indian Reservation in North Dakota and the Cheyenne River Indian Reservation in South Dakota.

"I hope that this discovery will ultimately lead to a Minnesota center for research on minority health issues that can deliver actual health benefits to these communities," Nelsestuen said.

Related Terms

Jennifer Jones looks incredulously around her. She does understand what is going on; she seems to be in a trance. Lying on a bed at the Mayo Clinic in Rochester, Minnesota, surrounded by machines that keep her balanced and with wires going in and out of her body, she will experience something new. And she is nervous. For the first time, she can breathe on her own after a lung transplant surgery.

The United States Food and Drug Administration (FDA) approved a vagus nerve stimulator for the treatment of migraines in adults, which is called gammaCore. The portable device is placed on the vagus nerve in the neck, releasing a slight electrical stimulation to the afferent nerve fibers. gammaCore relieves migraine pain from the outside.

Social insects like bees and ants can help us develop new drugs against antibiotic-resistant bacteria. This is due to the fact that they have developed alternative strategies to defend themselves against the higher exposure to pathogens associated with social life.

Experts share flu season is likely to be severe, making it important to get your flu shot, especially for those age 65 and above. EmaxHealth asked Dr. Adam Welch, Associate Professor at the Bill Gatton College of Pharmacy at East Tennessee State University and Gina Venditti MPAS, PA-C, Board of Trustees, Physician Assistant (PA) Foundation why it is so important for older adults to get an annual flu vaccine.

Anyone with a disability has likely suffered through questions that are - so to speak - truly insufferable. Some people are upfront about their disability and willing to share; while others may not have any visible signs. One should never assume. Here is a list of seven stupid and inappropriate things that people with disabilities have been asked.